Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). Cancer may affect people at all ages, but risk tends to increase with age. It is one of the principal causes of death in developed countries.
There are many types of cancer. Severity of symptoms depends on the site and character of the malignancy and whether there is metastasis. A definitive diagnosis usually requires the histologic examination of tissue by a pathologist. This tissue is obtained by biopsy or surgery. Most cancers can be treated and some cured, depending on the specific type, location, and stage. Once diagnosed, cancer is usually treated with a combination of surgery, chemotherapy and radiotherapy. As research develops, treatments are becoming more specific for the type of cancer pathology. Drugs that target specific cancers already exist for several types of cancer. If untreated, cancers may eventually cause illness and death, though this is not always the case.
Cancer can be treated by surgery, chemotherapy, radiation therapy, immunotherapy, monoclonal antibody therapy or other methods. The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient (performance status). A large number of experimental cancer treatments are also under development.
Complete removal of the cancer without damage to the rest of the body is the goal of treatment. Sometimes this can be accomplished by surgery, but the propensity of cancers to invade adjacent tissue or to spread to distant sites by microscopic metastasis often limits its effectiveness. The effectiveness of chemotherapy is often limited by toxicity to other tissues in the body. Radiation can also cause damage to normal tissue.
One problem with current methods for treating the various forms of cancer is the inability to detect how well a particular type of therapy is working. For example, neoadjuvant chemotherapy in the treatment of breast cancer produces significant clinical benefit to patients (PR+CR rates>70%) (see, e.g., Early Breast Cancer Trialists' Collaborative Group: Polychemotherapy for early breast cancer: An overview of the randomized trials. Lancet 352, 930-942, 1998) and can be used to increase the numbers of patients eligible for a breast preservation procedure. Neoadjuvant chemotherapy has the benefit of allowing observation of chemoresponsiveness, and biological evaluation of the cancer both before and after chemotherapy administration.
The ability to observe an individual's tumor response is of increasing importance in this time of rapid development of new and more targeted drugs against cancer. It is essential to determine which new drugs will benefit patients. However, clinical benefit is an endpoint that can take years to accurately determine, and therefore surrogate endpoints for clinical benefit are often used in the evaluation of new drugs. Because of its positive association with disease free survival, pathologic complete response to neoadjuvant chemotherapy has become a widely utilized surrogate endpoint for breast cancer regimens. Pathologic complete response can be evaluated approximately 3-6 months after treatment begins, but it would be useful to have a surrogate for clinical benefit that would be evaluable at an even earlier time point.
As such, improved techniques for evaluating the effectiveness of a particular treatment are needed. In addition, improved techniques designed to evaluate the effectiveness of a particular treatment during the course of the treatment are needed and would provide for individualization of treatments. This would save patients from systemic toxicity from ineffective treatment and reduce costs to the health care system. Thus, further, improved techniques for evaluating candidate therapies are needed.